School student inspired by animated proteins

We think of large molecules such as proteins as static objects. But actually they are dynamic, changing their shape. Rommie Amaro is using super computers to animate images of proteins. The results provide clues of new binding sites where other molecules can attach, such as new drugs. Rommie Amaro also describes the story of Eric Chen, the high school student who has won prestigious awards and has even had a paper published following work in Rommie Amaro’s lab.

Transcript

Robyn Williams: Let's though start with proteins. You like proteins, you're made of them, and this is the 100th year of crystallography, so we're looking at new ways to picture proteins and see how they interact. That already strikes you as complicated, confess! So why on earth would this sort of research attract a school kid and make him want to join in, with sensational results?

Meet Professor Rommie Amaro at the University of California, San Diego.

So here you have these very complicated molecules, and the way they work depends on their shape. And you're looking at the way they move around and might take up different aspects. How?

Rommie Amaro: That's right. So it turns out that we get these images of how these machines are and they very often are static images, but these are really dynamic moving machines.

Robyn Williams: You're calling proteins a machine?

Rommie Amaro: I am, yes.

Robyn Williams: That's bold.

Rommie Amaro: They are machines. They are the workhorses of the cell. So the function of these machines is really intimately tied to how they move and their dynamics.

Robyn Williams: How do you study that?

Rommie Amaro: So we are using just very simple physical equations where we can approximate the structure, the atomic structure of the molecule. And then we just integrate Newton's equation of motion over time essentially, and we do this on these supercomputers, these really, really large computers. We integrate these equations of motion millions and billions of times and then we can evolve a dynamic picture of how these proteins are actually moving.

Robyn Williams: So you animate them?

Rommie Amaro: Exactly.

Robyn Williams: And having animated them can you see them doing different things that you hadn't thought of before?

Rommie Amaro: Absolutely, that's the fun part. Discovering how they move and how that motion can be tied to function that either we know about or, for example in a lot of cases of these small molecules that we are now discovering, entirely new sites, new binding sites for drugs can actually reveal themselves in these computational simulations.

Robyn Williams: How long has this kind of work been going on?

Rommie Amaro: Well, the approach that we are doing is very, very new in terms of using the output of molecular simulation in a drug discovery program. There have been a lot of success in rational drug design for other targets, but to date we haven't had one that actually made it into a human yet, just because the timeline is so new, it's so long, and this is such a new technique. But we are pushing ahead on some very promising new cancer therapeutics, and so I'm hopeful that in the next 10 to 15 years hopefully we will be there.

Robyn Williams: Ten to 15? I'll come back in 10 to 15 months.

Rommie Amaro: I know, it's not fast enough, right? But it's the process, it's the process of actually getting a drug to market.

Robyn Williams: What happened when a young man knocked on your door?

Rommie Amaro: Oh, Eric, Eric Chen. Yes, so he knocked on my door and told me he was interested to do research. So I said okay, sure, I talked to him a little bit, he was in high school, young…

Robyn Williams: A high school boy.

Rommie Amaro: A high schooler, that's right.

Robyn Williams: A high school boy interested in proteins.

Robyn Williams: Yes, believe it or not! He's a rare one I guess. But he came and he was interested to do research and he seemed pretty determined. So he came to see me and I said okay, sure, send me an email, and he did. I probably didn't reply the first time, but he sent another one, and so I sent him a few papers and then he came back, and that relationship sort of took off.

He went to a summer school that I have here at the university to sort of learn some of the basic techniques, and I actually had assigned him a project. I said okay, you're going to look at this protein and cell signalling, and he did. And then after those eight weeks he came into my office, he said, 'Dr Amaro, I have an idea for a new project.' And I said, all right, I knew things had been going pretty well. So I said, okay. And he said, 'I really want us to come up with a new drug for the flu.' So influenza, obviously we hear about this all the time, and even now there are new strains all the time, so he was really interested in coming up with some drugs for it.

So he had identified a protein called endonuclease which when it's blocked, when its activity is blocked it basically stops viral replication. So it already had early indications of being a very good target. And again, since he is young and he's in high school I said, okay, if you're interested, go for it.

So he went off, and he did talk with people in my group and so forth for some technical guidance, but he came up with a set of molecules, small molecule compounds…so what we do is we take these protein structures and we can screen them or develop models of them that we can then use to possibly discover new drugs, and so that's exactly what he did. And he came with a set of compounds. And normally I have to say in my lab it sort of stops there, and at that point I call up a collaborator or I email someone who actually does bench work and I say, okay, we have some compounds, would you like to test them? And they do.

But Eric actually decided he wanted to run the assays too, he wanted to do the experiments. Fearless kid, just fearless. And so he knocked around on different labs and he was able to get into the Department of Pathology and run the assays, validated that these compounds actually worked. And that was kind of the story taking off. And then he also registered for a number of science fairs, and he used this work as a platform to win the Google Science Fair.

Robyn Williams: He won the Google Science Fair?

Rommie Amaro: He did, the grand champion, yes.

Robyn Williams: At the age of what?

Rommie Amaro: I guess he's 17.

Robyn Williams: 17? You're kidding!

Rommie Amaro: 16, 17, yes, he is young. It's amazing. And then a few months later he won the Siemens competition which is one of the most prestigious international science competitions, even bigger money kitty. So he is just sort of sweeping…and, I have to say, as a scientist I especially proud of…he has a first author publication in ACS Medicinal Chemistry Letters. So he has that also…he made it into the literature.

Robyn Williams: Before leaving school.

Rommie Amaro: Yes, in high school, it's really just phenomenal.

Robyn Williams: I find that very interesting because most of the remarkable young people I hear about are young women, and having a young man with the confidence to do that is, may I say, exceptional.

Rommie Amaro: It is exceptional. I mean, he is just really an incredibly…just has such initiative, and, like I said, he's just fearless. He will just try new things and knock on people's doors to take it all the way to the end. I think he has a very bright future ahead of him.

Robyn Williams: And he's a swimming champion and he sings like Justin Bieber and…

Rommie Amaro: Probably, probably a virtuoso, yes! I think he does fencing. Yes, a lot of skills.

Robyn Williams: Well, that shows you that an academic at your level should always open the door and always follow up the emails because bright young people may come and make all the difference.

Rommie Amaro: I think so, absolutely, that's part of our job, right?

Robyn Williams: Thank you.

Rommie Amaro: Thank you, this was a lot of fun, thank you.

Robyn Williams: And this is aforementioned Eric. What made you knock on the door of a professor and want to join in?

Eric Chen: I don't know, my love for science started when I was just a little kid actually, and I was really, really curious. And I guess I soon found that science had the answers to the questions that I had. And as I grew older I kind of realised science actually doesn't have all the answers, there is this entire field of research devoted to answering questions we haven't answered before, and that's what really got me interested in research. I thought it would be the coolest thing ever to be able to discover something no one has ever found before, and that's what really got me into it I guess.

Robyn Williams: How did you know you'd be good at it?

Eric Chen: I didn't! I thought it would be something I'd want to try out, and it really took off from there.

Robyn Williams: May I ask you how old you are now?

Eric Chen: Right now I'm 17 years old.

Robyn Williams: You're still 17. How do you deal with the successes you've had, these prizes?

Eric Chen: I don't know, I've been very honoured with what I've been able to accomplish. Of course I've been very surprised whenever I get one of them. But I've been very, very busy I guess, because I'm not at school a lot of the time to go to this outreach event or that talking event, and my teachers and mentors have all been very supportive of me and I'm really grateful for it.

Robyn Williams: What did your fellow high school students say? Where they excited, were they dismissive?

Eric Chen: They were definitely excited. A lot the students…the friends I had before, they were always very supportive, and even after I won these awards it didn't really change the relationship between us and I felt that was nice, and we still help each other out and maybe I'll say, 'Can I present this,' or, 'Can I practice this presentation to you,' and they'll say, 'Of course.'

Robyn Williams: I'm assuming you'll follow it up and go to university and study science and all the rest of it, but, you know, the really crucial question is; when you were so young, as you said just before, what really made all the difference to encourage you? Was it your parents, was it your teacher, was it things you observed, or what?

Eric Chen: Partly it was because of my parents because they are in science, and because of that I got the early influences where I could…I had maybe a toy microscope or this textbook lying around and I'd read through it. But it was also just I guess my observation, as I mentioned before. I found that a lot of these questions, the answers were all scientific. And because of my curiosity, that's what really deepened my interest for science.

Robyn Williams: And what do you plan to do?

Eric Chen: Oh gosh! In the future I guess I'd either like to become a college professor, I actually really love teaching as well and this would let me pursue both my passions for research and teaching. Or I'd like to become an entrepreneur because doing this research, it's really shown me the difference between discovering something in a lab and getting it to the market, to the consumers. And I think it would be really cool to bring these scientific innovations to those who need it.

Robyn Williams: At the age of 17. Congratulations.

Eric Chen: Thank you.

Robyn Williams: Eric Chen, who last week won the $100,000 Intel science grand prize, awarded in Washington DC. He has also won the Google International grand prize and the Siemens Foundation science prize, and I'm told he has been offered a place at Harvard. And, get this; he's considering it.

Before Eric you heard Professor Rommie Amaro at the University of California, San Diego, and she's also a star.